Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats

Doperalski, Nicholas J.; Sandhu, Milap S; Bavis, Ryan W.; Reier, Paul J.; Fuller, David D.

doi:10.1016/j.resp.2008.06.005

Cited by 45 publications

(33 citation statements)

References 39 publications

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“…These procedures were adapted from our prior publications (9,14,17,29,41). Isoflurane anesthesia (3-4% in O 2) was induced in a closed chamber followed by intraperitoneal injection of urethane (1.6 g/kg; Sigma, St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Dougherty

Lee

Lane

et al. 2012

Journal of Applied Physiology

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Dougherty BJ, Lee KZ, Lane MA, Reier PJ, Fuller DD. Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats. J Appl Physiol 112: 96-105, 2012. First published October 27, 2011 doi:10.1152/japplphysiol.00690.2011Spinal cord hemisection at C2 (C2HS) severs bulbospinal inputs to ipsilateral phrenic motoneurons causing transient hemidiaphragm paralysis. The spontaneous crossed-phrenic phenomenon (sCPP) describes the spontaneous recovery of ipsilateral phrenic bursting following C2HS. We reasoned that the immediate (next breath) changes in tidal volume (VT) induced by ipsilateral phrenicotomy during spontaneous breathing would provide a quantitative measure of the contribution of the sCPP to postinjury VT. Using this approach, we tested the hypothesis that the sCPP makes more substantial contributions to VT when respiratory drive is increased. Pneumotachography was used to measure VT in anesthetized, spontaneously breathing adult male rats at intervals following C2HS. A progressive increase in VT (ml/breath) occurred over an 8 wk period following C2HS during both poikilocapnic baseline breathing and hypercapnic respiratory challenge (7% inspired CO2). The sCPP did not impact baseline breathing at 1-3 days postinjury since VT was unchanged after ipsilateral phrenicotomy. However, by 2 wk post-C2HS, baseline phrenicotomy caused a 16 Ϯ 2% decline in VT; a comparable 16 Ϯ 4% decline occurred at 8 wk. Contrary to our hypothesis, the phrenicotomy-induced declines in VT (%) during hypercapnic respiratory stimulation did not differ from the baseline response at any postinjury time point (all P Ͼ 0.11). We conclude that by 2 wk post-C2HS the sCPP makes a meaningful contribution to VT that is similar across different levels of respiratory drive. plasticity; hemisection; phrenicotomy; cervix SEVERING IPSILATERAL BULBOSPINAL inputs to phrenic motoneurons via lateral hemisection of the C2 spinal cord (C2HS) transiently paralyzes the hemidiaphragm (22,23,27,48). However, a partial return of ipsilateral phrenic motoneuron inspiratory bursting occurs over a period of weeks to months following C2HS (14,15,20,37). This response has been termed the spontaneous crossed-phrenic phenomenon (sCPP; Refs. 22,28,40). The sCPP provides an important experimental model of neuroplasticity and associated functional recovery (i.e., phrenic bursting) after spinal cord injury (22,28,40). However, the functional contribution of the sCPP to ventilation (V E) has not been definitively established. In other words, it is unclear if the relatively small amount of electrical activity that has been measured in the ipsilateral phrenic nerve after chronic C2HS is sufficient to alter inspiratory tidal volume (V T ). Thus it is unknown if C2HS-induced, spontaneous neuroplastic changes associated with the sCPP (22, 23) have a meaningful impact on the respiratory system (20).The functional impact of the sCPP has been examined to a limited extent (14,15,20). Correlations between phrenic nerve activity ...

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Section: Methodsmentioning

confidence: 99%

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Dougherty

Lee

Lane

et al. 2012

Journal of Applied Physiology

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“…Breathing frequency has been reported to be higher in male than in female rats (19,20). ERa, ERb, and the androgen receptor are expressed in respiratory motor neurons of male and female rats (21) and intraventricular infusion of an ERa antisense vector was shown to decrease brain ERa protein levels and to affect ventilation in rats of both sexes (22).…”

Section: Sex Differences In Respiratory Physiologymentioning

confidence: 99%

Hormonal Influences on Lung Function and Response to Environmental Agents: Lessons from Animal Models of Respiratory Disease

Card¹,

Zeldin²

2009

Proceedings of the American Thoracic Society

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Numerous studies in humans and experimental animals have identified considerable sex differences in respiratory physiology and in the response of the lung to environmental agents. These differences appear to be mediated, at least in part, by sex hormones and their nuclear receptors. Moreover, animal models are increasingly used to study pathogenic mechanisms and test potential therapies for a variety of human lung diseases, many of which appear to be influenced by sex and sex hormones. In this article, data are summarized from studies of lung function and disease in which sex differences have been observed. Specific attention is paid to animal models of acute lung injury, nonallergic and allergic lung inflammation, and lung fibrosis. It is anticipated that continued investigation of the role of sex and sex hormones in animal models will provide valuable insight into the pathogenesis and potential treatments for a variety of acute and chronic human lung diseases.

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“…In support of this hypothesis, a comparison of male and female rodents with SCI indicated that female rats and mice showed less tissue damage and improved hindlimb locomotor function compared to male cohorts (Farooque et al, 2006;Hauben et al, 2002). Similarly, in a model of cervical SCI, female rats showed improved respiratory recovery compared to male or ovariectomized counterparts (Doperalski et al, 2008). Several studies have reported that 17b-estradiol administration reduces secondary injury and promotes functional recovery after SCI, but the dosing and administration timing vary substantially between studies.…”

mentioning

confidence: 92%

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

Kachadroka

Hall

Niedzielko

et al. 2010

Journal of Neurotrauma

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Several groups have recently shown that 17b-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17b-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17b-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17b-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5-or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax=Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17b-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonadintact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17b-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17b-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

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Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats

Cited by 45 publications

References 39 publications

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Hormonal Influences on Lung Function and Response to Environmental Agents: Lessons from Animal Models of Respiratory Disease

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

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